Process for producing bipyridyls



United States Patent 3,210,362 PROCESS FOR PRODUCING BIPYRIDYLS Alastair Campbell and Ralph Santorre Fanshawe, Widnes, England, assignors to Imperial Chemical Industries Limited, Millbank, London, England, a corporation of Great Britain No Drawing. Filed Sept. 6, 1962, Ser. No. 221,899 Claims priority, application Great Britain, Sept. 12, 1961, 32,711/61 21 Claims. (Cl. 260-496) This invention relates to a process for the manufacture or organic bases, and more particularly for the manufacture of bipyridyls.

4:4-bipyridyl is a valuable intermediate for herbicidal materials, but the methods so far available for making it have the disadvantage of producing mixtures of isomeric bipyridyls from which the desired 4:4-isomer has to be separated. The method of making this material by interacting sodium and pyridine and then oxidising the sodium-pyridine interaction product, in particular, also has the disadvantage that sodium metal is extremely reactive, and very careful control of the reaction is necessary.

We have now found that bipyridyls can be made by interacting aluminium and a pyridine and oxidising the aluminium-pyridine interaction product thus obtained. This process has the advantage of producing 4:4-bipyridyl with only very small proportions of the undesired isomeric bipyridyls.

Thus according to the present invention we provide a process for the manufacture of bipyridyls which comprises interacting aluminium and a pyridine, and oxidising the aluminium-pyridine interaction product so formed.

The aluminium may be used in any convenient form, and preferably one having a large surface area, for example turnings, foil or powder. Pure aluminium or an alloy of aluminium containing minor proportions of other metals may be used. Alloys of aluminium with other pyridine-reactive metals (for example magnesium or sodium) may be used with economic advantage as then the alloying metal can take part in the interaction, even when present in high proportions. The surface of the metal should be as clean as possible to facilitate interaction.

The interaction of the aluminium and the pyridine is usually slow to start, apparently due in part to the inert oxide film usually present on the surface of aluminium, and is preferably started by a small proportion of an initiator in the pyridine-aluminium mixture. Suitable initiators include materials which assist in breaking down this surface oxide film and materials which can induce the formation of free radicals in the aluminium-pyridine mixture. Mercury and its compounds, particularly mercuric chloride, are especially suitable examples of compounds which can break down the surface oxide film.

Examples of materials which can induce the formation of free radicals in the aluminium-pyridine mixture include in particular the alkali metals (for example, lithium, sodium and potassium), the more active alkaline earth metals (calcium, strontium and barium) and the halogens (particularly bromine and iodine). When the initiator is a metal, it is most conveniently used in the form of a finely ground or dispersed form, preferably in some inert diluent which prevents oxidation of the metal surface and preserves it in an active state. When the initiator is a halogen, it may be added as such or as a solution, for example in an inert diluent or in the pyridine. It is preferred to use a dispersion of sodium or potassium as initiator, since these materials are especially efiicient and readily available. Such dispersions may be readily prepared by known methods, for example by mechanical or ultrasonic agitation of the molten metal in an inert diluent. The inert diluent may be selected so as to have a boiling point which is convenient in the preparation of the dispersion or in the subsequent operations. Suitable diluents include liquid (or readily melted) hydrocarbons, for example petroleum fractions and alkylated benzenes.

As mercury and its compounds do not, in general, promote vigorous interaction, we especially prefer to use a combination of initiators of the two types described above (i.e., an oxide film breaker and a free radical former). When using both types of initiator, however, we prefer to add the oxide film breaker first so that it can function to some degree before the free radical former is added.

The proportion of initiator to be used may vary considerably. In general, appropriate proportions are at least 2%, and preferably at least 5% by weight of the aluminium present in the mixture to be interacted. Larger proportions may be necessary in some cases, for example when the metal is not clean or when the pyridine-metal mixture is not dry, and proportions of 20% or more of the aluminium present may be required in extreme circumstances. The upper limit is largely dependent upon economic considerations and the speed of interaction required. Smaller proportions may suflice in some cases, for example when the reactants are very pure. A metal-pyridine interaction product is also effective as an initiator so that, once the interaction has commenced, further additions of metal and/ or the pyridine may be made without necessarily requiring more initiator. Thus, reaction can be initiated by the presence of a small proportion of an aluminimum-magnesium alloy reacting with pyridine. Reaction of the magnesium alloy can be initiated by the presence of a small proportion of magnesium and a free radical forming initiator such as sodium, potassium, bromine or iodine.

The interaction between the aluminium and the pyridine may conveniently be carried out at temperatures up to the reflux temperature (i.e., boiling point of the interaction mixture, usually about C. at normal atmospheric pressure) though the interaction tends to be inconveniently slow below 60 C. Higher or lower interaction temperatures may be used if desired, however. It is usually most convenient to carry out the interaction at atmospheric pressure, but higher or lower pressures may be used if desired.

The time required for the interaction varies with the particular materials and interaction conditions employed, and is longer when lower interaction temperatures are used. Interaction may be completed in as little as 30 minutes or as long as ten or twelve hours.

The interaction may be carried out in the presence of a diluent, which is preferably a solvent for the bipyridyls and for the aluminium-pyridine interaction product. An excess of the pyridine can be used as this: solvent diluent. This avoids any possible coating of the aluminium with any of the reaction products which would prevent further reaction.

The course of the reactions taking place during the proccess of the present invention is not clear. It appears that at least three molecular proportions of the pyridine are required for each atomic proportion of aluminium consumed in the interaction, though an excess of the pyridine is preferably used for example as a diluent. Accordingly, the proportion of the pyridine used may be up to 15, and preferably between 5 and 15 molar proportions for each atomic proportion of aluminium. Larger proportions may be used if desired, but this is less economical because of the larger proportion of unreacted pyridine to be recovered. Interaction may be discontinued, if desired, before all the aluminium present has been consumed. Any unreacted aluminium or pyridine remaining need not necessarily be removed before oxidation of the interaction product takes place.

The mechanism of the oxidation of the aluminiumpyridine interaction product is especially obscure, so we use the term oxidation in the sense of including any process which effects removal of hydrogen or electrons from the aluminium-pyridine interaction product. The oxidation may be carried out by means of oxygen, or mixtures thereof with an inert diluent gas for example nitrogen. This can be carried out by bubbling oxygen, for example in the form of air or some other mixture of oxygen and nitrogen, through the interaction product while it is stirred vigorously by means of a mechanical stirrer to promote thorough gas-liquid contact. We have found that the oxidation may also be carried out using chlorine, alone or in admixture with an inert diluent gas. The oxidation can also be carried out by adding hypochlorites, nitric acid (as free acid or neutralised with an organic base such as a pyridine), or a water-soluble inorganic peroxy compound (particularly hydrogen peroxide), conveniently in the form of aqueous solutions.

The oxidation may be carried out at any desired temperature. The optimum temperature in any particular instance and the time required for the oxidation to be completed will depend for example upon the oxidation conditions employed and may be determined by simple trial. The oxidation conditions should not be made so vigorous that the bipyridyls themselves are lost by excessive oxidation. Completion of the oxidation is usually indicated conveniently by the consumption of a calculated amount of an oxidising agent, by further reaction ceasing, or by a change in colour of the reaction mixture (usually from dark blue to brown).

We have found that it is preferable to reduce the viscosity of the reaction mixture during the oxidation step by adding a liquid diluent, usually before commencing the oxidation. If this is not done, a gelatinous mixture is usually formed during the oxidation which may prevent further oxidation taking place. Such a diluent may be water, for example in the proportion of two parts of water to each part of aluminium used; other suitable diluents include alcohols for example methanol, and hydrocarbons for example petroleum fractions and alkylated benzenes. It may be advantageous to select the diluent to as to avoid wastage or the formation of undesirable byproducts, for example by reaction with any oxidising agent such as chlorine.

Commonly a mixture of isomeric bipyridyls is produced by the process of the present invention, the principal constituents being the 2:2'-, 2:4'- and 4:4'-isomers or such of these as are permitted by the structure of the pyridine used as starting material. The 4:4'-isomer usually predominates. Pyridine itself gives a product which is mainly 4:4-bipyridyl, with only 210% of 2:4-bipyridyl and in which 2:2-bipyridyl is seldom detected at all.

The pyridine for use in the process of the present invention should be as free as possible from any substituent or impurity (for example, piperidine) which can take part in any undesirable side-reaction with the metal or the initiator. The process is especially applicable to pyridine itself .Pyridines containing hydrocarbon radicals (particularly alkyl radicals, for example methyl and/or ethyl radicals) may also be used, for example picolines and lutidines, though these are much less reactive than pyridine itself.

The bipyridyls may be isolated from the product resulting from the oxidation step by known methods, for example fractional distillation under reduced pressure, extraction with organic solvents, or combinations of such techniques. The method to be used may vary according to whether the product desired is the mixture of all the bipyridyls produced in the reaction, or particular isomers. In general, the bipyridyls may be freed first from most of the excess pyridine and any volatile diluent used by a preliminary distillation at atmospheric pressure, and then from terpyridyls and other materials by fractional distillation under reduced pressure. If desired, the reaction mixture may be extracted with a solvent in order to eliminate any aluminium hydroxide present, before or after any preliminary distillation, and this solvent then removed by distillation; suitable solvents for this purpose include methylene chloride and benzene.

4:4-bipyridyl itself may be isolated in substantially pure form by way of its hydrochloride from the mixture of bipyridyls produced from pyridine. This may conveniently be done by dissolving the mixed bipyridyls in hot methanol, treating this solution with dry hydrogen chloride, cooling the solution so that 4:4'-bipyridyl hydrochloride separates out, removing this solid hydrochloride by filtration, and converting the hydrochloride to free 4:4-bipyridyl by treatment with an alkali, for example potassium bicarbonate, sodium carbonate or caustic soda. Alternatively, the mixed bipyridyls may be converted to hydrochlorides, for example by solution in ether and treatment with dry hydrogen chloride, and the mixed hydrochlorides then washed with methanol or ethanol to free the 4:4'-bipyridyl dihydrochloride from the more soluble isomers. Higher polypyridyls, for example terpyridyls, do not interfere with this method of purification, so that the mixed polypyridyls may be extracted directly from the oxidation product with a solvent, for example, ether, and the 4:4'-bipyridyl dihydrochloride isolated as described above. 2:4'-bipyridyl may be extracted by making use of its greater solubility in water or its higher volatility when distilled with solvents, for example methylene chloride, benzene or pyridine.

The process of the present invention has the advantages of rapid reaction and ease of control with excellent yields of bipyridyls without the need for using a highly reactive alkali metal such as sodium to form the interaction product. Furthermore the oxidation step in the process of the present invention may be carried out smoothly and easily without any interference due to the formation of a gelatinous reaction mixture. This is of particular importance when the process is being worked on a commercial scale.

The bipyridyls thus produced are useful as intermediate products in chemical synthesis, as for example in the manufacture of agricultural chemicals and the like.

The invention is illustrated but not limited by the following examples in which the parts and percentages are by weight.

Example 1 Aluminium foil (13.5 g., 0.5 atom) was heated under reflux with pyridine g.) and mercuric chloride (0.25 g.) and as soon as reaction had started a further 137 g. pyridine, to make a total of 3 mols pyridine, was added. The mixture was refluxed for six hours under a stream of nitrogen then a further 158 g. (2 mols) of pyridine were added and refluxing was continued for a further four hours. Water (27 g.) was added to reduce the viscosity of the product and it was oxidised at 70 C. by blowing in a stream of air at a rate of 20 l./ hr. for five hours. The total product weighed 410 g. and contained 20.1 g, 4:4- bipyridyl, less than 0.5 g. of 2:4'-bipyridyl and no detectable 2:2'-isomer.

Example 2 Aluminum powder (40.5 g., 1.5 atoms) was heated under reflux with pyridine (300 g., 3.8 mols) and mercuric chloride (1.5 g.) in a stirred flask continuously purged with nitrogen. The mixture was then refluxed for 10 hours, and 1210 g. (15.3 mols) of pyridine were added in portions as required throughout this period to keep the contents of the flask in a fluid state. The product was then cooled and oxidised at 60 C. with 50 litres/hr. of air until the black colour of the mixture was discharged. The product weighed 1494 g. and contained 100 g. 4:4-bipyridyl, 2.5 g. of 2:4'-bipyridyl and no detectable 2:2'-isomer.

Example 3 Aluminium foil (5.0 parts, 0.185 atom) was heated with pyridine (100 parts, 1.27 mole) under reflux conditions. 1 part of a sodium dispersion (33% sodium metal in trimethylbenzene), 0.25 part of magnesium raspings and 0.25 part of a powdered alloy containing 50% magnesium and 50% aluminium were added and the mixture was refluxed in a stream of nitrogen for 90 minutes. Pyridine (50 parts) was then added and refluxing was continued for 30 minutes more, and then another 50 parts of pyridine were added and the refluxing was continued up to a total of 5 hours. 50 parts of pyridine were then added, and the mixture was oxidised at 60 C. by adding 15.2 parts of an aqueous 15% solution of sodium hypochlorite. The total product (268 parts) contained 10.5 parts of 4:4'-bipyridyl, 0.3 part of 2:4-bipyridyl and no detectable amount of 2:2'-isomer.

Example 4 A powdered alloy containing 50% aluminium and 50% magnesium (13.5 parts) was heated with pyridine (100 parts, 1.27 mole) under reflux conditions. 1 part of a sodium dispersion (33% sodium metal in trimethylbenzene) and 0.5 part of magnesium raspings were added and the mixture was refluxed in a stream of nitrogen for 5 hours. A further 50 parts of pyridine were then added and refluxing was continued for 3 hours more, and then 50 parts more of pyridine were added and the total mixture was oxidised at 80 C. by adding 54.6 parts of an aqueous 15% solution of sodium hypochlorite. The total product (260 parts) contained 22.4 parts of 4:4'-bipyridyl, 1.5 parts of 2:4'-bipyridyl and 1.5 parts of 2:2-bipyridyl.

Example 5 A mixture of aluminium powder g.) and dry pyridine (440 g.) was heated under refluxing conditions, interaction was initiated by addition of mercuric chloride (2 g.) followed 5 minutes later by sodium (1 g. in the form of a 33% dispersion in trimethylbenzene), and refluxing was continued for 5.5 hours. The resulting mixture was then treated with sodium hypochlorite (25 g. of an aqueous solution). The product contained 18 g. of 4:4'-bipyridyl, corresponding to an efliciency of 21% on the aluminium used and 23% on the pyridine used.

Repetition of the procedure of this example using mercuric chloride (2 g.) and sodium (2 g. in the form of a 33% dispersion in trimethylbenzene) as initiators, gave a reaction product containing 24.4 of 4:4'-bipyridyl, corresponding to an efliciency of 29% on the aluminium used and 31% on the pyridine used.

Repetition of the procedure of this example using as initiator sodium (4 g. in the form of a 33% dispersion in trimethylbenzene) but no mercuric chloride, gave a reaction product containing 6.3 g. of 4:4-bipyridyl, corresponding to an efliciency of 7% on the aluminium or the yridine used.

Example 6 A mixture of aluminium powder (10 g.) and pyridine (528 g.) was heated under refluxing conditions for 2.5 hours after initiation of interaction by mercuric chloride (1 g.) and sodium (2 g. as a 33% dispersion in trimethylbenzene). A stream of air/nitrogen mixture 1:1) was then blown through the reaction mixture for 6 hours. The resulting product contained 21.6 g. of 4:4'-bipyridyl, corresponding to an efliciency of 25% on the aluminium used or 26% on the pyridine used.

Example 7 Interaction of a mixture of pyridine (399 g.) and aluminium powder (10 g.) was initiated by addition of mercuric chloride (3 g.), and was continued for 3.75 hours at reflux. The mixture was then oxidised by blowing a current of an air-nitrogen mixture (1:1) through it as in Example 6. The resulting product, weighed approxi- Example 8 Interaction of a mixture of pyridine (400 parts) and aluminium powder 10 parts) was initiated by addition of mercuric chloride (1 part) followed by sodium (1 part), and then the mixture was refluxed. for 6 hours and finally oxidised by blowing in a stream of an air-nitrogen mixture (1:1) as in Example 6. The resulting product was treated with water (40 parts) and then fractionally distilled, first at atmospheric pressure to give pyridine (319 parts )and then at 1 to 2 mm. pressure to give a crude 'bipyridyl fraction (25 parts) from which pure 4:4'-bipyridyl (16 parts) was isolated by crystallisation from petrol ether.

Example 9 A mixture of 10 parts of aluminum powder and 400 parts of pyridine was refluxed for 2.75 hours after inter action had been initiated by addition of 3 parts of mercuric chloride, and the resulting mixture was oxidised by blowing in a stream of an air-nitrogen mixture (1:1) as in Example 6. Analysis of the resulting product by gas-liquid chromatography showed that it contained 17 parts of 4:4-bi-pyridyl, corresponding to an efliciency of 19% based on the aluminium used or 22% based on the pyridine used.

Repetition of the procedure of this example, using as initiator 1.5 parts of mercuric chloride and 1.5 parts of sodium, gave a product which was found by analysis to contain 28.4 parts of 4:4'-bipyridyl, corresponding to an eflicency of 32% based on the aluminium used or 34% based on the pyridine used.

Example 10 A mixture of aluminium powder (10 parts) and pyridine (444 parts) was heated at C. for 2 hours after interaction had been initiated with mercuric chloride (2 parts) and sodium (2 parts). The resulting mixture was then oxidised by addition of nitrobenzene parts). The final product thus obtained was found to contain 24 parts of 4:4-bipyridyl, corresponding to an efliciency of 27.4% based on the aluminium used and 34.4% based on the pyridine consumed.

. Repetition of the procedure of this example except that the aluminium-pyridine interaction was carried out for 17 hours at 30 C. and that the oxidation step was carried out by addition of 66 parts of nitrobenzene, gave 17.3 parts of 4:4-bipyridyl, corresponding to an efliciency of 20% on the aluminium used and 29% on the pyridine used.

Example 1] Interaction time 1 hour 4.5 hours 24 hours Pyridine used (parts) 352 528 528 4:4-lo 1pyridyl formed (parts) 8 9. 9 12. 7 Efiie eney on aluminium (percent) 9 11 15 Efileiency on pyridine (percent) 18 12 18 '2' Example 12 Interaction of aluminium powder (10 parts) and pyridine (399 parts) was initiated with mercuric chloride (3 parts) and was continued at 116 C. for 3.75 hours. The interaction mixture was then oxidised by passing through it a stream of an air-nitrogen mixture (1:1) as in Example 6. Analysis of the product showed that the product contained 14.3 parts of 4:4-bipyridyl, corresponding to 16% efficiency on the aluminium or 17.4% efiiciency on the pyridine consumed.

The procedure of this example was repeated except that 150 parts of pyridine were used, and 150 parts of NzN-dimethylaniline were added to the interacting mixture after initiation of the interaction. The 4:4-bipyridyl formed was found to be 1.7 parts, corresponding to 2% efficiency on the aluminium or 7% efficiency of the pyridine used.

The procedure was again repeated using a mixture of 150 parts of pyridine and 250 parts of N:N-dimethylaniline in place of the 399 parts of pyridine. The 4:4- bipyridyl thus formed was found to be 2.9 parts, corre sponding to an efliciency of 3% on the aluminium or of the pyridine used.

What we claim is:

1. In process for preparing a 4:4-bipyridyl by interacting a metal with pyridine in the presence of an initiator, followed by the oxidation of the resulting interaction product to give said bipyridyl, the improvement which comprises utilizing aluminium as the metal for interaction with the pyridine whereby the bipyridyl product obtained after oxidation is predominantly 4:4- bipyridyl.

2. Process as claimed in claim 1 wherein the interaction of the pyridine and the aluminium is initiated by a material selected from the group consisting of mercury and its compounds.

3. Process as claimed in claim 2 wherein there is used mercuric chloride as initiator.

4. Process as claimed in claim 1 wherein the interaction of the pyridine and the aluminium is initiated by a material selected from the group consisting of an alkali metal, an alkaline earth metal, and a halogen.

5. Process as claimed in claim 4 wherein there is used an alkali metal as initiator.

6. Process as claimed in claim 5 wherein there is used a dispersion of potassium as initiator.

7. Process as claimed in claim 5 wherein there is used a dispersion of sodium as initiator.

8. Process as claimed in claim 4 wherein there is used a halogen as initiator.

9. Process as claimed in claim 8 wherein there is used bromine as initiator.

10. Process as claimed in claim 1 wherein the interaction of the pyridine and the aluminium is initiated first by a material selected from the group consisting of mercury and its compounds, and then by a material selected from the group consisting of an alkali metal, an alkaline earth metal and a halogen.

11. Process as claimed in claim 2 wherein the proportion of initiator is at least 2% by weight of the aluminium present in the mixture to be interacted.

12. Process as claimed in claim 11 wherein the proportion of initiator is at least 5% by weight of the aluminium present in the mixture to be interacted.

13. Process as claimed in claim 1 wherein the interaction is carried out at a temperature in the range C. to C.

14. Process as claimed in claim 1 wherein the interaction is carried out in the presence of a diluent which is a solvent of bipyridyl and an aluminium-pyridine interaction product.

15. Process as claimed in claim 14 wherein the diluent is an excess of the pyridine.

16. Process as claimed in claim 1 wherein the oxidation is carried out by a member selected from the group consisting of oxygen and a mixture of oxygen with an inert diluent gas.

17. Process as claimed in claim 1 wherein the oxidation is carried out with chlorine.

18. Process as claimed in claim 1 wherein the oxidation is carried out in the presence of a liquid diluent which reduces the viscosity of the mixture.

19. Process as claimed in claim 18 wherein the liquid diluent is water.

20. Process as claimed in claim 8 wherein there is used iodine as initiator.

21. A process for preparing 4:4-bipyridyl which comprises interacting pyridine and aluminium in the presence of excess pyridine as diluent and from 2 to 5% by weight of an initiator, based on the weight of aluminium, the interaction being carried out at a temperature between about 60 C. and the boiling point of the interaction mixture, and then oxidizing the resulting interaction product with oxygen to form an oxidation product consisting primarily of said 4:4-bipyridyl and thereafter recovering the 4:4-bipyridyl from said oxidation product.

References Cited by the Examiner UNITED STATES PATENTS 2,773,066 12/56 Linnell et al. 260296 3,040,052 6/62 Judd 260296 WALTER A. MODANCE, Primary Examiner.

JOHN D. RANDOLPH, NICHOLAS S. RIZZO,

Examiners. 

1. IN PROCESS FOR PREPARING A 4:4''-BIPYRIDYL BY INTERACTING A METAL WITH PYRIDINE IN THE PRESENCE OF AN INITIATOR, FOLLOWED BY THE OXIDATION OF THE RESULTING INTERACTION PRODUCT TO GIVE SAID BIPYRIDYL, THE IMPROVEMENT WHICH COMPRISES UTILIZING ALUMINIUM AS THE METAL FOR INTERACTION WITH THE PYRIDINE WHEREBY THE BIPYRIDYL PRODUCT OBTAINED AFTER OXIDATION IS PREDOMINANTLY 4:4''BIPYRIDYL. 